The Yasui procedure with a modified right ventricle-to-pulmonary artery connection utilizing autologous left atrial appendage as a free graft.

A 9-month-old girl born with an interrupted aortic arch type B, an arteria lusoria (aberrant right subclavian artery) and a multilevel left ventricular outflow tract obstruction underwent a Yasui completion after an initial interim palliation. After the Damus-Kaye-Stansel procedure was carried out and the Sano shunt had been established as a source of pulmonary flow, the reported procedure comprised closure of the ventricular septal defect and the intraventricular baffling of left ventricular outflow through a malaligned ventricular septal defect, incision and partial resection of a conal septum and establishment of a right ventricle-to-pulmonary artery connection using an autologous left atrial appendage as a free graft. This technique consisted of dissecting and harvesting the left atrial appendage, which was then used as autologous material for an interposition plasty connecting the central pulmonary artery bifurcation segment with the upper rim of the infundibulotomy. Native, autologous tissue thus comprised the backwall of the newly created right ventricle-to-pulmonary artery continuity. Porcine pericardial patch plasty was then used to complete the remaining circumference of the right ventricle-to-pulmonary artery continuity.

Ex Vivo Allograft Perfusion for Complex Pediatric Heart Transplant Recipients.

BACKGROUND: Pediatric heart transplant (HTx) recipients with congenital heart defects require complex concomitant surgical procedures with the risk of prolonging the allograft's ischemic time. Ex vivo allograft perfusion with the Organ Care System (OCS; Transmedics, Andover, MA) may improve survival of these challenging patients. METHODS: In this retrospective, single-center study a consecutive series of 8 children with allografts preserved using the OCS was compared with 13 children after HTx with cold storage of the donor heart from March 2018 to March 2020. RESULTS: Median recipient age in the control group was 18 months (range, 1-189) versus 155 months (range, 83-214) in the OCS group, and the baseline differences between the 2 groups were not significant. Fifty percent of the children in the OCS group had complex congenital heart defects (vs 15% of the control subjects). Median operation time during HTx in the OCS group was 616 minutes (range, 270-809) versus 329 minutes (range, 283-617). Because of the time of ex vivo allograft perfusion (265 minutes [range, 202-372]) median total ischemia time was significantly shorter in the OCS group: 78 minutes (range, 52-111) versus 222 minutes (range, 74-326). The incidence of primary graft, renal, or hepatic failure did not differ between the groups. Graft function and the occurrence of any treated rejection at follow-up revealed no significant difference between the 2 groups. One-year survival was 88% in the OCS group (vs 85%). CONCLUSIONS: Ex vivo allograft perfusion enabled complex pediatric HTx, yielding outcomes as positive as those of children whose donor hearts were stored in ice-cold solution.

Multitrait analysis of glaucoma identifies new risk loci and enables polygenic prediction of disease susceptibility and progression.

Glaucoma, a disease characterized by progressive optic nerve degeneration, can be prevented through timely diagnosis and treatment. We characterize optic nerve photographs of 67,040 UK Biobank participants and use a multitrait genetic model to identify risk loci for glaucoma. A glaucoma polygenic risk score (PRS) enables effective risk stratification in unselected glaucoma cases and modifies penetrance of the MYOC variant encoding p.Gln368Ter, the most common glaucoma-associated myocilin variant. In the unselected glaucoma population, individuals in the top PRS decile reach an absolute risk for glaucoma 10 years earlier than the bottom decile and are at 15-fold increased risk of developing advanced glaucoma (top 10% versus remaining 90%, odds ratio = 4.20). The PRS predicts glaucoma progression in prospectively monitored, early manifest glaucoma cases (P = 0.004) and surgical intervention in advanced disease (P = 3.6 × 10-6). This glaucoma PRS will facilitate the development of a personalized approach for earlier treatment of high-risk individuals, with less intensive monitoring and treatment being possible for lower-risk groups.

Echocardiographic characteristics in Fontan patients before the onset of protein-losing enteropathy or plastic bronchitis.

BACKGROUND: It was this study's objective to evaluate the echocardiographic characteristics and flow patterns in abdominal arteries of Fontan patients before the onset of protein-losing enteropathy (PLE) or plastic bronchitis (PB). DESIGN: In this retrospective cohort investigation, we examined 170 Fontan patients from 32 different centers who had undergone echocardiographic and Doppler ultrasound examinations between June 2006 and May 2013. Follow-up questionnaires were completed by 105 patients a median of 5.3 (1.5-8.5) years later to evaluate whether one of the complications had occurred since the examinations. RESULTS: A total of 91 patients never developed PLE or PB ("non-PLE/PB"); they were compared to 14 affected patients. Eight of the 14 patients had already been diagnosed with "present PLE/PB" when examined. Six "future PLE/PB" patients developed those complications later on and were identified on follow-up. The "future PLE/PB" patients presented significantly slower diastolic flow velocities in the celiac artery (0.1 (0.1-0.5) m/s vs 0.3 (0.1-1.0) m/s (P = .04) and in the superior mesenteric artery (0.0 (0.0-0.2) m/s vs 0.2 (0.0-0.6) m/s, P = .02) than the "non-PLE/PB" group. Median resistance indices in the celiac artery were significantly higher (0.9 (0.8-0.9) m/s vs 0.8 (0.6-0.9) m/s, (P = .01)) even before the onset of PLE or PB. CONCLUSION: An elevated flow resistance in the celiac artery may prevail in Fontan patients before the clinical manifestation of PLE or PB.

Refractive, corneal and ocular residual astigmatism: distribution in a German population and age-dependency - the Gutenberg health study.

PURPOSE: Worldwide, the most frequent cause of visual impairment is uncorrected refractive error. This analysis focused on the distribution and associations of refractive, corneal and ocular residual astigmatism. METHODS: As part of the Gutenberg Health study, a population-based cross-sectional study was conducted in the general population of Germany. A comprehensive ophthalmological examination including refraction, tonometry, and Scheimpflug imaging of the anterior cornea (Pachycam) was performed. In addition to the magnitude and type (with-the-rule, against-the-rule, oblique) of the refractive or corneal astigmatism, we calculated the vector components (J0, J45) of both astigmatisms and calculated the ocular residual astigmatism. We performed multiple quantile regression analysis to evaluate the factors associated with refractive, corneal and ocular residual astigmatisms. RESULTS: A total of 13,558 subjects (49% female) with a mean age of 54.0 years (range 35-74 years) were included in this study. The prevalence of refractive astigmatism (>1.0D) was 13.0% in right eyes and 12.0% in left eyes, and 85% of these subjects wore spectacles. The distribution of refractive astigmatism showed a two-peak distribution with high astigmatism for with-the-rule and against-the-rule astigmatism. The associated factors were corneal curvature, age and sex for the different astigmatisms (p < 0.001). CONCLUSIONS: We analyzed the prevalence of different astigmatisms within a European population. We confirmed a shift with aging from with-the-rule to against-the-rule astigmatism to refractive and corneal astigmatism. Astigmatism has a large impact on visual perception; more than 85% of people with astigmatism over one diopter wore glasses for distance vision.

Percutaneous Pulmonary Valve Implantation in the Patched Right Ventricular Outflow Tract 51 Years after Surgical Repair for Tetralogy of Fallot.

Percutaneous pulmonary valve implantation (PPVI) has become a widely practiced treatment option for patients with right ventricular outflow tract (RVOT) dysfunction. For this procedure, the Melody transcatheter pulmonary valve has become the most widely used system. On-label indications are limited to the treatment of failing circumferential conduits. However, there is growing but still limited experience with the off-label treatment of native or patched RVOTs. Here, the case is reported of a 57-year-old patient in whom redo-surgery for a dysfunctional pulmonary valve could be avoided by PPVI into the patched RVOT at 51 years after tetralogy of Fallot repair.

Prevalence and Cardiovascular Associations of Diabetic Retinopathy and Maculopathy: Results from the Gutenberg Health Study.

OBJECTIVE: Diabetic retinopathy (DR) is the leading cause of blindness in people of working age. The purpose of this paper is to report the prevalence and cardiovascular associations of diabetic retinopathy and maculopathy (DMac) in Germany. RESEARCH DESIGN AND METHODS: The Gutenberg Health Study (GHS) is a population-based study with 15,010 participants aged between 35 at 74 years from the city of Mainz and the district of Mainz-Bingen. We determined the weighted prevalence of DR and DMac by assessing fundus photographs of persons with diabetes from the GHS data base. Diabetes was defined as HbA1c ≥ 6.5%, known diagnosis diabetes mellitus or known diabetes medication. Furthermore, we analysed the association between DR and cardiovascular risk factors and diseases. RESULTS: Overall, 7.5% (1,124/15,010) of the GHS cohort had diabetes. Of these, 27.7% were unaware of their disease and thus were newly diagnosed by their participation in the GHS. The prevalence of DR and DMac was 21.7% and 2.3%, respectively among patients with diabetes. Vision-threatening disease was present in 5% of the diabetic cohort. In the multivariable analysis DR (all types) was associated with age (Odds Ratio [95% confidence interval]: 0.97 [0.955-0.992]; p = 0.006) arterial hypertension (1.90 [1.190-3.044]; p = 0.0072) and vision-threatening DR with obesity (3.29 [1.504-7.206]; p = 0.0029). DR (all stages) and vision-threatening DR were associated with duration of diabetes (1.09 [1.068-1.114]; p<0.0001 and 1.18 [1.137-1.222]; p<0.0001, respectively). CONCLUSIONS: Our calculations suggest that approximately 142 000 persons aged between 35 and 74 years have vision threatening diabetic retinal disease in Germany [corrected].Prevalence of DR was lower in the GHS compared to East-Asian studies. Associations were found with age, arterial hypertension, obesity, and duration of diabetes mellitus.

Myopia and level of education: results from the Gutenberg Health Study.

PURPOSE: To analyze the association between myopia and educational level in an adult European cohort. DESIGN: Population-based cross-sectional study. PARTICIPANTS: A cohort of the Gutenberg Health Study, including 4658 eligible enrollees between 35 and 74 years of age. METHODS: We applied a standardized protocol entailing a comprehensive questionnaire; thorough ophthalmic, general, cardiovascular, and psychological examinations; and laboratory tests, including genetic analyses. We documented achievement levels in school education and post-school professional education. The spherical equivalent (SE) was determined by noncycloplegic autorefractometry. We fitted mixed linear models including age, gender, and 45 myopia-associated single nucleotide polymorphisms (SNP) as covariates. MAIN OUTCOME MEASURES: Prevalence and magnitude of myopia in association with years spent in school and level of post-school professional education. RESULTS: Individuals who graduated from school after 13 years were more myopic (median, -0.5 diopters [D]; first quartile [Q1]/third quartile [Q3], -2.1/0.3 D) than those who graduated after 10 years (median, -0.2 D; Q1/Q3, -1.3/0.8 D), than those who graduated after 9 years (median, 0.3 D; Q1/Q3, -0.6/1.4 D), and than those who never finished secondary school (median, 0.2 D; Q1/Q3, -0.5/1.8 D; P<0.001, respectively). The same holds true for persons with a university degree (median, -0.6 D; Q1/Q3, -2.3/0.3 D) versus those who finished secondary vocational school (median, 0 D; Q1/Q3, -1.1/0.8 D) or primary vocational school (median, 0 D; Q1/Q3, -0.9/1.1 D) versus persons without any post-school professional qualification (median, 0.6 D; Q1/Q3, -0.4/1.7 D; P<0.001, respectively). Of persons who graduated from school after 13 years, 50.9% were myopic (SE, ≤-0.5 D) versus 41.6%, 27.1%, and 26.9% after 10 years, in those who graduated after 9 years, and in those who never graduated from secondary school, respectively (P<0.001). In university graduates, the proportion of myopic persons was higher (53%) than that of those who graduated from secondary (34.8%) or primary (34.7%) vocational schools and than in those without any professional training (23.9%; P<0.001, respectively). In multivariate analyses: higher school and professional levels of education were associated with a more myopic SE independent of gender. There was a small effect of age and SNPs. CONCLUSIONS: Higher levels of school and post-school professional education are associated with a more myopic refraction. Participants with higher educational achievements more often were myopic than individuals with less education.

Correlations between central corneal thickness and general anthropometric characteristics and cardiovascular parameters in a large European cohort from the Gutenberg Health Study.

PURPOSE: The aim of this study was to evaluate the correlations between general anthropometric features and cardiovascular parameters and central corneal thickness (CCT) in an adult European cohort. METHODS: Analysis was based on a Gutenberg Health Study cohort that included 5000 subjects (2540 male, 2460 female), aged 35 to 74 years at enrollment. The participants underwent a standardized protocol with a comprehensive questionnaire; ophthalmic examination (slit-lamp biomicroscopy; autorefractometry; noncontact tonometry; fundus photography; CCT measurements (optical pachymetry); visual field testing; and a thorough general examination focused on cardiovascular parameters, psychosomatic evaluation, and laboratory tests including genetic analysis. RESULTS: Reliable CCT measurements were available for 4708 right eyes (OD, 94.2%), 4721 left eyes (OS, 94.4%), and both eyes (OU) in 4698 subjects (94.0%). The mean CCT was 555 ± 35 µm in men and 549 ± 35 µm in women. In multiple linear regression analysis, the CCT was associated with gender [P < 0.001 for OU], body height [in men, P = 0.007 for OD, P = 0.04 for OS; in women P < 0.001 for OU], and body mass index (P < 0.001 for OD, P = 0.001 for OS). In men only, the CCT correlated with the body weight [P = 0.024 (OD), P = 0.048 (OS)] and smoking [P = 0.006 (OD), P < 0.001 (OS)]. No correlations were found between the CCT and dyslipidemia, diabetes, or hypertension. CONCLUSIONS: The CCT was associated with male gender, body height, and body mass index in an adult white cohort. It correlated with body weight and nicotine abuse in men only. No associations were found between the CCT and dyslipidemia, diabetes, or hypertension.

Prevalence of age-related macular degeneration in a large European cohort: results from the population-based Gutenberg Health Study.

BACKGROUND: The aim of this study was to describe the sex- and age-specific prevalence of age-related macular degeneration (AMD) and its correlation with urban or rural residence in a large and relatively young European cohort. METHODS: We evaluated fundus photographs from participants in the Gutenberg Health Study (GHS), a population-based, prospective, observational, single-centre study in the Rhineland-Palatine region in midwestern Germany. The participants were 35-74 years of age at enrolment. The fundus images were classified as described in the Rotterdam Study and were graded independently by two experienced ophthalmologists (CK and UBK) based on the presence of hard and soft drusen, retinal pigmentary abnormalities, and signs of atrophic or neovascular age-related macular generation (AMD). RESULTS: Photographs from 4,340 participants were available for grading. Small, hard drusen (<63 µm, stages 0b and 0c) were present in 37.4% of participants (95% confidence interval [CI], stage 0b, 31.6% [30.3-33.7]; stage 0c, 5.8% [5.1-6.5]). Early AMD (soft drusen, pigmentary abnormalities, stages 1-3) was present in 3.8% of individuals in the youngest age group (35-44 years) (95% CI, stage 1a, 0.4% [0.3-0.5%]; stage 1b, 3.2% [2.9-3.5%]; stage 2a, 0.1% [0.1-0.2%]; stage 2b, 0% [0-0.0%]; stage 3, 0.1% [0.1-0.2%]), whereas late AMD (stages 4a and 4b) did not appear in the youngest age group. In all age groups, signs of early AMD were detected in 11.9% of individuals (stage 1a, 2.1% [1.7-2.6]; stage 1b, 8.0% [7.2-8.8]; stage 2a, 1.0% [0.7-1.3]; stage 2b, 0.5% [0.3-0.7]; stage 3, 0.3% [0.2-0.6]). Late AMD (geographic atrophy or neovascular AMD) was found in 0.2% of individuals (stage 4a, 0.1 % [0.0-0.2]; stage 4b, 0.1% [0.0-0.2]). AMD increased significantly with age (odds ratio [OR], 1.09; 95% CI, 1.08-1.10). Sex, iris colour, and residence (rural vs. urban) were not associated with different rates of AMD. CONCLUSIONS: In this study, the prevalence of AMD increased dramatically with age; however, although AMD is usually thought to occur after age 50, signs of early AMD were found in 3.8% of individuals in the youngest age group (younger than 45 years). This population-based sample is the first to provide substantial epidemiologic data from a large German cohort, including data on macular degeneration in younger age groups and incidence data after recall.

Distribution of central corneal thickness and its association with ocular parameters in a large central European cohort: the Gutenberg health study.

MAIN OBJECTIVE: To evaluate the distribution of central corneal thickness (CCT) in a large German cohort and to analyse its relationship with intraocular pressure and further ocular factors. DESIGN: Population-based, prospective, cohort study. METHODS: The Gutenberg Health Study (GHS) cohort included 4,698 eligible enrollees of 5,000 subjects (age range 35-74 years) who participated in the survey from 2007 to 2008. All participants underwent an ophthalmological examination including slitlamp biomicroscopy, intraocular pressure measurement, central corneal thickness measurement, fundus examination, and were given a questionnaire regarding glaucoma history. Furthermore, all subjects underwent fundus photography and visual field testing using frequency doubling perimetry. RESULTS: Mean CCT was 557.3 ± 34.3 µm (male) and 551.6±35.2 µm in female subjects (Mean CCT from right and left eyes). Younger male participants (35-44 years) presented slightly thicker CCT than those older. We noted a significant CCT difference of 4 µm between right and left eyes, but a high correlation between eyes (Wilcoxon test for related samples: p<0.0001). Univariable linear regression stratified by gender showed that IOP was correlated with CCT (p<0.0001). A 10 µm increase in CCT led to an increase in IOP between 0.35-0.38 mm Hg, depending on the eye and gender. Multivariable linear regression analysis revealed correlations between gender, spherical equivalent (right eyes), and CCT (p<.0001 and p=0.03, respectively). CONCLUSIONS: We observed positive correlations between CCT and IOP and gender. CCT was not correlated with age, contact lens wear, positive family history for glaucoma, lens status, or iris colour.

Distribution of intraocular pressure and its association with ocular features and cardiovascular risk factors: the Gutenberg Health Study.

PURPOSE: To describe the distribution of intraocular pressure (IOP) and its association with ocular features and cardiovascular risk factors in an adult European cohort. DESIGN: Population-based, cross-sectional study. PARTICIPANTS: This analysis was based on a Gutenberg Health Study (GHS) cohort that included 4335 eligible enrollees from among 5000 subjects who participated in the survey from 2007 through 2008. The age range was 35 to 74 years at enrollment. METHODS: Participants underwent a standardized protocol with a comprehensive questionnaire; ophthalmic examination including slit-lamp biomicroscopy, noncontact tonometry, fundus photography, central corneal thickness measurement, and visual field testing; and a thorough general examination focused on cardiovascular parameters, psychological evaluation, and laboratory tests, including genetic analysis. MAIN OUTCOME MEASURES: Mean and reference interval of IOP stratified by age, gender, and eye. RESULTS: Mean ± standard deviation (SD) IOP was 14.0 ± 2.6 mmHg in both eyes, 13.9 ± 2.7 mmHg in right eyes, and 14.0 ± 2.7 mmHg in left eyes. Mean ± SD IOP in men (n = 2216) and in women (n = 2119) was 14.1 ± 2.7 mmHg and 13.9 ± 2.5 mmHg with an intersex difference (P = 0.009). Positive univariate associations with higher IOP were detected for brown iris color, central corneal thickness, hypertension, diabetes, smoking, obesity, dyslipidemia, body mass index, weight, hip size (women only), waist circumference, and waist-to-hip ratio. Multivariate testing revealed male gender, central corneal thickness, brown iris color, hypertension, smoking, and waist-to-hip ratio to be correlated with higher IOP. In women, age correlated negatively with IOP in the multivariate analysis. CONCLUSIONS: Intraocular pressure distribution in this cohort yielded a lower mean IOP than in similar white study populations. Increasing age in women correlated with lower IOP. Association analyses with several systemic characteristics revealed that cardiovascular risk factors correlated with higher IOP. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Genome-wide association analyses identify multiple loci associated with central corneal thickness and keratoconus.

Central corneal thickness (CCT) is associated with eye conditions including keratoconus and glaucoma. We performed a meta-analysis on >20,000 individuals in European and Asian populations that identified 16 new loci associated with CCT at genome-wide significance (P < 5 × 10(-8)). We further showed that 2 CCT-associated loci, FOXO1 and FNDC3B, conferred relatively large risks for keratoconus in 2 cohorts with 874 cases and 6,085 controls (rs2721051 near FOXO1 had odds ratio (OR) = 1.62, 95% confidence interval (CI) = 1.4-1.88, P = 2.7 × 10(-10), and rs4894535 in FNDC3B had OR = 1.47, 95% CI = 1.29-1.68, P = 4.9 × 10(-9)). FNDC3B was also associated with primary open-angle glaucoma (P = 5.6 × 10(-4); tested in 3 cohorts with 2,979 cases and 7,399 controls). Further analyses implicate the collagen and extracellular matrix pathways in the regulation of CCT.

Population-based meta-analysis in Caucasians confirms association with COL5A1 and ZNF469 but not COL8A2 with central corneal thickness.

Central corneal thickness (CCT) has become an endophenotype of major interest for the genetically complex disorder glaucoma. CCT has a high heritability, and thin CCT is an independent risk factor for the diagnosis and progression of open-angle glaucoma. Genome-wide association studies thus provide genetic loci associated with CCT and potentially related to open-angle glaucoma. The distribution of CCT and prevalence of glaucoma in population-based studies have demonstrated ethnic differences suggesting ethnic-dependent variations in the genetic determinants of CCT. We conducted a genome-wide association study in Caucasians (n = 3,931) from the Gutenberg Health Study (Germany) followed by replication of 30 genome-wide significant SNPs or SNPs of interest (P < 10(-5)) in the Rotterdam Study (The Netherlands, n = 1,418). In a combined analysis, we confirmed quantitative trait loci on chromosomes 9q34 and 16q24 for association with CCT. On chromosome 16q24, the locus is located in an intergenic region near the ZNF469 gene (top SNP: rs9938149, P = 1.45 × 10(-12)). ZNF469 missense mutation is involved in a syndrome with very thin cornea (brittle cornea syndrome). The second locus on chromosome 9q34 represents the intergenic region between the RXRA and COL5A1 gene (top SNP: rs3132306, P = 2.71 × 10(-10)). Collagen type 5 determines the diameter of the corneal collagen fibrils. In our Caucasian population-based GWA study, we reinforce the involvement of collagen-related genes influencing CCT in Caucasians. We could not confirm the collagen type 8 locus on chromosome 1 as reported in Asian studies.

Anti-tumor necrosis factor alpha for retinal diseases: current knowledge and future concepts.

Tumor necrosis factor alpha (TNF-α) is a pro-inflammatory cytokine produced by macrophages and T-cells. It plays an important role both in inflammation and apoptosis. In the eye, TNF-α appears to have a role in the pathogenesis of inflammatory, edematous, neovascular and neurodegenerative disorders. Several TNF-blocking drugs have been developed and approved, and are in clinical use for inflammatory diseases such as rheumatoid arthritis, psoriasis and ankylosing spondylitis. TNF-α blockers are widely used in ophthalmology as an off-label alternative to "traditional" immunosuppressive and immune-modulatory treatments in noninfectious uveitis. Preliminary studies suggest a positive effect of intravenously administered TNF-α blockers, mainly infliximab, for treating refractory diabetic macular edema and neovascular age-related macular degeneration. Unfortunately, much of the current data raises considerable safety concerns for intravitreal use of TNF-α inhibitors, in particular, intraocular inflammatory responses have been reported after intravitreal injection of infliximab. Results of dose-finding studies and humanized antibody or antibody fragments (e.g. adalimumab) are anticipated in the coming years; these will shed light on potential benefits and risks of local and systemic TNF-α blockers used for treatment of diseases of the retina and choroid.

Influence of Fe(II) and Fe(III) on the expression of genes related to cholesterol- and fatty acid metabolism in human vascular smooth muscle cells.

Iron is the major alloy component for a large variety of cardiovascular devices such as stents. In recent studies it has been shown that biodegradable iron or iron based stents exhibit good mechanical features with no pronounced neointimal proliferation. Whole genome gene profiling using DNA chip technology revealed that genes involved in cholesterol and fatty acid metabolism (low-density lipoprotein receptor, LDL-R; 3-hydroxy-3-methylglutaryl-Coenzyme A synthase 1 (HMGCS1) and fatty acid desaturase 1 (FADS1) are up-regulated after exposure of vascular smooth muscle cells with soluble ferrous iron. To analyze the effects of iron on these genes in detail we co-incubated human vascular smooth muscle cells for 12 and 24 h with different concentrations of ferrous (soluble iron(II)-gluconate) and ferric iron (soluble iron(III)-chloride), Ferrlecit, a commercially available drug (ferric iron-gluconate complex) and solid iron coils. The expression of LDL-R, HMGCS1 and FADS1 was analyzed using TaqMan Real-time PCR. After 24 h, all forms of iron led to a significant up-regulation of the examined genes. At high concentrations the expression rates declined, probably as a result of reduced metabolic activity. The most prominent effects were observed after co-incubation with Ferrlecit, probably caused by an increased bioavailability of the iron gluconate complex. We postulate that both, bi- and trivalent forms of iron induce the expression of LDL-R, HMGCS1 and FADS1 by generation of highly reactive oxygen species. Further animal experiments using tissues from iron-stented vessels may lead to a more profound insight into iron induced expression of cholesterol- and fatty acid metabolism related genes.

Development and biocompatibility of a novel corrodible fluoride-coated magnesium-calcium alloy with improved degradation kinetics and adequate mechanical properties for cardiovascular applications.

Recently, corrodible magnesium-based alloys have been introduced for use as cardiovascular stents and orthopedic implants. However, rapid corrosion rates have raised questions about their biocompatibility. Therefore, we developed a binary fluoride-coated magnesium-calcium alloy with improved degradation kinetics. Biocompatibility of the alloys was evaluated with metabolic assays (colorimetric WST-1 test). Furthermore, five different probes of magnesium-calcium alloys (MgCa 0.4, 0.6, 0.8, 1.2, and 2.0 wt %) were cocultivated with human smooth muscle cells and endothelial cells. To investigate the decomposition kinetics in a physiological environment the alloys were used untreated and fluoride coated (MgF(2)). Mg and Ca decreased the metabolic activity in vascular cells dose-dependently, with cytotoxic effects only at unphysiological concentrations. Uncoated magnesium alloys showed signs of decomposition after a short incubation time of 24 h in contrast to MgF(2) coated alloys. After 10 days smooth muscle and endothelial cells around the alloys were still alive, whereas colonization of the surfaces was only observed for smooth muscle cells. The fluoride-coated MgCa alloys exhibited good results concerning mechanical properties, degradation kinetics, and biocompatibility in vitro. We conclude that a binary fluoride magnesium-calcium alloy is a promising candidate for the production of cardiovascular stents.